scholarly journals Effect of Musk Tongxin Dropping Pill on Myocardial Remodeling and Microcirculation Dysfunction in Diabetic Cardiomyopathy

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Jingjing Zhao ◽  
Yan Zhou ◽  
Huahua Liu ◽  
Zhaohai Zheng ◽  
Shuqing Liu ◽  
...  

Objective. To explore the effect of Musk Tongxin Dropping Pill (MTDP) on myocardial remodeling and microcirculation dysfunction in diabetic cardiomyopathy (DCM). Methods. Forty male SD rats were randomly divided into control group (control group, n = 10), DCM model group (DCM group, n = 10), DCM model + pioglitazone group (DCM + PLZ group, n = 10), and DCM model + MTDP group (DCM + MTDP group, n = 10). An intraperitoneal single injection of 65 mg/kg streptozotocin (STZ) was used to establish rat model of DCM and the rats in control group were treated with the same dose of sodium citrate buffer solution. DCM + PLZ group was treated with 3 mg/kg/d PLZ by ig after modeling, DCM + MTDP group was treated with 22 mg/kg/d MTDP by ig, and DCM group was treated with 2 ml/kg/d sodium carboxymethyl cellulose (CMC-Na) by ig. The general condition of rats was continuously observed. After intervening for 3 weeks, the random blood glucose of rats was detected by tail vein, and the echocardiography examination was performed. Blood specimens were collected from the abdominal aorta, serum nitric oxide (NO) and endothelin-1 (ET-1) were detected to estimate endothelial function, and tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), IL-1β, malondialdehyde (MDA), and superoxide dismutase (SOD) were detected to observe the changes of inflammation and oxidative stress indexes. The heart mass index (HMI) was calculated through the ratio of heart mass (HM) to the corresponding body mass (BM). Myocardial pathological tissue staining was performed. Results. Compared with control group, blood glucose in other three groups was higher. Left ventricular end systolic diameter (LVSD) and left ventricular end diastolic diameter (LVDD) in DCM group showed a significant increase, while left ventricular ejection fraction (LVEF) and heart rate (HR) in this group displayed an obvious decrease P < 0.01 . BM and HM in DCM group exhibited a reduction, and HM/BM × 103 revealed an apparent increase P < 0.01 . The levels of serum NO and SOD were distinctly downregulated P < 0.01 , and the levels of ET-1, MDA, TNF-α, IL-1β, and IL-6 were remarkably upregulated P < 0.01 . Compared with DCM group, a significant decrease was observed in LVSD and LVDD in DCM + MTDP group, while LVEF and HR obviously increased P < 0.05 . BM and HM indicated an apparent increase, but HM/BM ×103 reduced distinctly P < 0.01 . The levels of serum NO and SOD were markedly upregulated P < 0.05 , and the levels of ET-1, MDA, TNF-α, IL-1β, and IL-6 were significantly downregulated P < 0.05 . HE staining showed that myocardial cells arranged neatly in the control group but not in the DCM group. The intercellular space between myocardial cells in DCM group increased, accompanied by damage of myocardial fibers and infiltration of inflammatory cells. Masson staining displayed an increase in interstitial collagen fibers in DCM group. Carstairs staining showed that microembolization occurred in the myocardium in DCM group, while in DCM + MTDP and DCM + PLZ groups the corresponding myocardial pathological changes were significantly improved. Conclusions. MTDP might show a positive effect on myocardial remodeling and microcirculation dysfunction in DCM rats.

2020 ◽  
Vol 23 (2) ◽  
pp. E234-E238
Author(s):  
Liting Zhang ◽  
Dan Chen ◽  
Min Peng ◽  
Hongbo Ma

Objective: To study the effects of Yixintai pills on myocardial cell apoptosis in rats with adriamycin (ADR)-induced heart failure (HF) and the mechanism of action. Methods: Sixty healthy male Wistar rats randomly were divided into Control, Model, Captopril, and Yixintai pill groups. A rat model of ADR-induced HF was constructed by intraperitoneal injection of ADR (2.5 mg/kg). The control group was given an equal volume of normal saline; the Yixintai pill and Captopril groups were given corresponding mediations (5 mg/kg) by lavage. After 4 weeks of treatment, fasting blood was collected to detect the contents of plasma rennin activity (PRA), angiotensin II (AngII), and aldosterone (ALD). B ultrasound was used to detect the heart structure, and the heart weight/body weight (HW/BW) ratio was calculated. The pathology of myocardial tissues was observed by HE staining. The apoptosis of myocardial cells was detected by TUNEL assay. The expression levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in serum were analyzed by ELISA, and the protein expression levels of protein kinase B (Akt), phosphorylated (p)-Akt, glycogen synthase kinase-3β (GSK-3β) and p-GSK-3β in myocardial tissues were measured by Western blotting. Results: Compared with the Control group, the PRA, AngII, ALD, left ventricular posterior wall thickness at end-systole (LVPWs), left ventricular posterior wall thickness at end-diastole (LVPWd), interventricular septal thickness at end-systole (IVSs), interventricular septal thickness at end-diastole (IVSd), HW/BW, TNF-α and IL-6 of model group increased significantly (P < .05). PRA, AngII, ALD, LVPWs, LVPWd, IVSs, IVSd, HW/BW, TNF-α and IL-6 of the Yixintai pill and Captopril groups were significantly lower than those of the Model group (P < .05). There were no significant differences in the indices between the Yixintai pill and Captopril groups (P > .05). In the Model group, lamellar necrosis, vacuolar degeneration, increased myocardial fibers and lamellar dissolution of myocardial cells were found in myocardial tissues. However, the myocardial cells of the Control group were neatly arranged and clearly structured, and only a few ones underwent fibrosis. There were mild myocardial fibrosis and vacuolar degeneration in the Yixintai pill and Captopril groups, and the degeneration and hyperplasia of myocardial fibers were obviously relieved. Compared with the Control group, the apoptosis index (AI) of the Model group increased significantly (P < .05). The AI values of the Yixintai pill and Captopril groups were significantly lower than those of the Model group (P < .05). Compared with the Control group, the expression levels of p-Akt and p-GSK-3β in the Model group decreased significantly (P < .05). The expression levels of p-Akt and p-GSK-3β in the Yixintai pill and Captopril groups were significantly higher than those of the Model group (P < .05), whereas the former 2 groups had similar results (P > 0.05). Conclusion: Yixintai pills may inhibit myocardial cell apoptosis and ventricular remodeling in rats by up-regulating PI3K/Akt/GSK-3β signal, thus protecting the heart function.


2020 ◽  
Vol 20 (7) ◽  
pp. 1117-1132
Author(s):  
Abdelaziz M. Hussein ◽  
Elsayed A. Eid ◽  
Ismaeel Bin-Jaliah ◽  
Medhat Taha ◽  
Lashin S. Lashin

Background and Aims: In the current work, we studied the effects of exercise and stevia rebaudiana (R) extracts on diabetic cardiomyopathy (DCM) in type 2 diabetic rats and their possible underlying mechanisms. Methods: : Thirty-two male Sprague Dawley rats were randomly allocated into 4 equal groups; a) normal control group, b) DM group, type 2 diabetic rats received 2 ml oral saline daily for 4 weeks, c) DM+ Exercise, type 2 diabetic rats were treated with exercise for 4 weeks and d) DM+ stevia R extracts: type 2 diabetic rats received methanolic stevia R extracts. By the end of the experiment, serum blood glucose, HOMA-IR, insulin and cardiac enzymes (LDH, CK-MB), cardiac histopathology, oxidative stress markers (MDA, GSH and CAT), myocardial fibrosis by Masson trichrome, the expression of p53, caspase-3, α-SMA and tyrosine hydroxylase (TH) by immunostaining in myocardial tissues were measured. Results: T2DM caused a significant increase in blood glucose, HOMA-IR index, serum CK-MB and LDH, myocardial damage and fibrosis, myocardial MDA, myocardial α-SMA, p53, caspase-3, Nrf2 and TH density with a significant decrease in serum insulin and myocardial GSH and CAT (p< 0.05). On the other hand, treatment with either exercise or stevia R extracts significantly improved all studied parameters (p< 0.05). Moreover, the effects of stevia R was more significant than exercise (p< 0.05). Conclusion: Both exercise and methanolic stevia R extracts showed cardioprotective effects against DCM and Stevia R offered more cardioprotective than exercise. This cardioprotective effect of these lines of treatment might be due to attenuation of oxidative stress, apoptosis, sympathetic nerve density and fibrosis and upregulation of the antioxidant transcription factor, Nrf2.


2015 ◽  
Vol 309 (10) ◽  
pp. H1621-H1628 ◽  
Author(s):  
Timoteo Marchini ◽  
Verónica D'Annunzio ◽  
Mariela L. Paz ◽  
Lourdes Cáceres ◽  
Mariana Garcés ◽  
...  

Inflammation plays a central role in the onset and progression of cardiovascular diseases associated with the exposure to air pollution particulate matter (PM). The aim of this work was to analyze the cardioprotective effect of selective TNF-α targeting with a blocking anti-TNF-α antibody (infliximab) in an in vivo mice model of acute exposure to residual oil fly ash (ROFA). Female Swiss mice received an intraperitoneal injection of infliximab (10 mg/kg body wt) or saline solution, and were intranasally instilled with a ROFA suspension (1 mg/kg body wt). Control animals were instilled with saline solution and handled in parallel. After 3 h, heart O2 consumption was assessed by high-resolution respirometry in left ventricle tissue cubes and isolated mitochondria, and ventricular contractile reserve and lusitropic reserve were evaluated according to the Langendorff technique. ROFA instillation induced a significant decrease in tissue O2 consumption and active mitochondrial respiration by 32 and 31%, respectively, compared with the control group. While ventricular contractile state and isovolumic relaxation were not altered in ROFA-exposed mice, impaired contractile reserve and lusitropic reserve were observed in this group. Infliximab pretreatment significantly attenuated the decrease in heart O2 consumption and prevented the decrease in ventricular contractile and lusitropic reserve in ROFA-exposed mice. Moreover, infliximab-pretreated ROFA-exposed mice showed conserved left ventricular developed pressure and cardiac O2 consumption in response to a β-adrenergic stimulus with isoproterenol. These results provides direct evidence linking systemic inflammation and altered cardiac function following an acute exposure to PM and contribute to the understanding of PM-associated cardiovascular morbidity and mortality.


2009 ◽  
Vol 37 (06) ◽  
pp. 1059-1068 ◽  
Author(s):  
Min Ge ◽  
Shanfeng Ma ◽  
Liang Tao ◽  
Sudong Guan

The relationship between changes of cardiac function and the gene expressions of two major myocardial skeleton proteins, titin and nebulin, and the effect of gypenosides on these gene expressions in diabetic cardiomyopathy rat were explored in the present study. Forty Sprague-Dawley rats were randomly divided into three groups: control group, diabetic cardiomyopathy group and gypenosides-treated diabetic cardiomyopathy group. The diabetic cardiomyopathy was induced in rats by injecting streptozotocin (STZ, 55 mg/kg) intraperitoneally. Seven weeks after the rats suffered from diabetes, the rats were treated with gypenosides 100 mg/kg per day orally for six weeks in gypenosides-treated group. In the meanwhile, the pure water was given to diabetic cardiomyopathy and the control groups. Subsequently, the cardiac functions, including left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), ± dP/dtmax and t–dP/dmaxt, as well as the mRNA content and proteins of titin and nebulin in myocardium were determined. The results indicated that (1) the diabetic cardiomyopathy rats had decreased LVSP and ± dP/dtmax, increased LVEDP, and prolonged t–dP/dtmax than normal rats; (2) LVSP and ± dP/dtmax in diabetic cardiomyopathy rats treated with gypenosides were significantly higher and LVEDP and t–dP/dtmax were significantly lower than those without giving gypenosides; (3) the mRNA contents and proteins of titin and nebulin in diabetic cardiomyopathy rats were remarkably lower than those in the control rats and gypenosides had no effect on mRNA and protein expression levels of titin and nebulin in diabetic cardiomyopathy rats. We conclude that (1) the cardiac function as well as the mRNA expressions of titin and nebulin decreased in diabetic cardiomyopathy rats; (2) gypenosides secure cardiac muscles and their function from diabetic impairment and these beneficial effects of gypenosides are not by changing the expressions of titin and nebulin.


2019 ◽  
Vol 3 (2) ◽  
Author(s):  
Umut Kocabaş ◽  
Özgür Yılmaz ◽  
Volkan Kurtoğlu

Abstract Background Diabetic cardiomyopathy (DC) is defined as a ventricular diastolic and/or systolic dysfunction, which is directly related to diabetes mellitus (DM) in the absence of coronary artery disease, valvular, congenital or hypertensive heart disease, and alcoholism. In this report, we present an unusual case of a patient with DC and reversible, acute left ventricular systolic dysfunction due to cardiotoxicity of hyperosmolar hyperglycaemic state (HHS). Case summary A 20-year-old male patient presented with weakness and polyuria. Physical examination and electrocardiogram were normal. Laboratory results and arterial blood gas analysis were consistent with HHS. Baseline echocardiography showed global left ventricular hypokinesis with an ejection fraction (EF) of 36%. The patient’s clinical condition improved after blood glucose level normalization and echocardiography revealed progressive improvement in the left ventricular systolic function with an EF of 54% at the 5-day follow-up and an EF of 69% at the 15-day follow-up. Discussion Uncontrolled DM and hyperglycaemic crisis may result in cardiotoxicity, acute left ventricular systolic dysfunction, and DC. The pathophysiological mechanism of this phenomenon is still unclear. Blood glucose control is the most important strategy for the prevention of DC.


2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Baozhu Ding ◽  
Songyan Geng ◽  
Xiaojie Hou ◽  
Xuelian Ma ◽  
Huazhou Xu ◽  
...  

Objective. To observe the effect of berberine (BBR) on kidney cell pyroptosis in golden hamsters with diabetic nephropathy (DN) and to explore the molecular mechanism of its renal protection. Methods. Fifty clean-grade male golden hamsters were randomly divided into a control group (10) and a model building group (40). The DN model was established by high-sugar and high-fat feeding and injection of a small amount of STZ. After successful establishment of the model, they were randomly divided into a model group, western medicine group, and berberine high- and low-dose groups. The western medicine group was given irbesartan 13.5 mg/kg, and the berberine high- and low-dose groups were given BBR 200 mg/kg and 100 mg/kg, respectively, for 8 consecutive weeks. An automatic biochemical analyser was used to measure blood glucose, blood lipids, kidney function, MDA, and other indicators; radioimmunoassay was used to assess serum insulin; enzyme-linked immunosorbent assay (ELISA) was used to quantify IL-1β, IL-6, IL-18, TNF-α; HE, PAS, and Masson staining were used to observe kidney pathological tissue morphology; western blot and real-time fluorescent quantitative PCR were used to assess protein and mRNA expression of molecules, such as Nrf2, NLRP3, Caspase-1, and GSDMD; and TUNEL staining was used to detect DNA damage. SPSS statistical software was used for the data analysis. Results. The kidney tissues of golden hamsters in the control group were normal; Nrf2 was highly expressed, serum MDA level was low, NLRP3 expression in kidney tissue was not obvious, Caspase-1 and GSDMD were weakly expressed, and only a few TUNEL-positive cells were observed. Compared with the control group, the golden hamsters in the model group had obvious renal pathological damage; blood glucose, blood lipids, renal function-related indexes, insulin, and inflammatory factors IL-1β, IL-6, IL-18, and TNF-α were increased ( P < 0.05 ); NLRP3, Caspase-1, and GSDMD expression was increased; Nrf2 expression was decreased; MDA level was increased ( P < 0.05 ); and the number of TUNEL-positive cells was increased. Compared with the model group, the pathological morphology of the kidney tissue of golden hamsters in the three treatment groups was significantly improved; blood glucose, blood lipids, renal function, and the expression of inflammatory factors IL-1β and IL-6 were reduced ( P < 0.05 ); NLRP3, Caspase-1, GSDMD, and other molecular proteins and mRNA expression were decreased; Nrf2 expression was increased; MDA level was decreased ( P < 0.05 ); and the number of TUNEL-positive cells was decreased. Conclusion. DN golden hamster kidney NLRP3-Caspase-1-GSDMD signalling was enhanced. BBR can reduce oxidative stress damage by regulating antioxidative Nrf2 and then regulating NLRP3-Caspase-1-GSDMD signalling to inhibit pyroptosis, antagonizing DN inflammation-induced damage.


2004 ◽  
Vol 61 (3) ◽  
pp. 259-266
Author(s):  
Zoran Perisic ◽  
Mirko Burazor ◽  
Goran Radjen ◽  
Lazar Todorovic ◽  
Zorka Burazor ◽  
...  

The aim of this study was to evaluate clinical and echocardiographic characteristics of patients with diabetic cardiomyopathy. The study included 72 patients, divided into two groups. The experimental group consisted of 32 diabetics, while 40 gender and age-matched healthy subjects were in the control group. In the experimental group there were 17 patients with insulin-dependent diabetes mellitus, and 15 patients with non-insulin-dependent diabetes mellitus. The average duration of diabetes mellitus was 9.53 years. All the patients underwent the following diagnostic procedures: standard laboratory tests, 12-lead ECG, chest X-ray, 24-h Holter ECG, and complete echocardiographic examination. More frequent appearance of ventricular rhythm disturbances (65,6% vs. 47,5%), increased heart rate (78.3 ? 8.2 vs. 72.1 ? 4.6 beats per minute), and alteration of diastolic (56.25% vs. 12.5%) and systolic function (43.8% vs. 0%) was registered in patients with diabetes, compared to the control group. Experimental group was divided, according to their left ventricular dimensions, into two subgroups: the subgroup with normal left ventricular dimensions, and the subgroup with the increased left ventricular dimensions. Patients with the increased left ventricular dimensions not only had significantly lower ejection fraction (37.4 ? 7.0 vs. 61.3 ? 4.2%), but also had significantly longer duration of diabetes (12.6 ? 5.8 vs. 8.01 ? 3.01 years), worse quality of glycoregulation (13.1 ? 2.5 vs. 10.4 ? 2.1%), and higher Shapiro?s microvascular complications index (2.7 ? 1.26 vs. 0.68 ? 0.56). High degree of correlation was also found between the duration of diabetes left ventricular ejection fraction (-0.86), and left ventricular mass (0.86). The similar level of correlation was shown with Shapiro?s index (-0.77 and 0.88), as well as with morning glycaemia (-0.57 and 0.41). According to the obtained results it could be concluded that the changing rate of diabetic cardiomyopathy was in direct correlation with the quality of diabetes control, the duration of diabetes, and the presence of complications in other organs.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Chunmei Li ◽  
Miao Yuan ◽  
Kun Li ◽  
Wenjuan Bai ◽  
Li Rao

AbstractCardiovascular disease is one of the main causes of death in diabetes mellitus (DM) patients. The aim of the current study was to explore the value of peak strain dispersion (PSD) for discovering early-stage left ventricular (LV) dysfunction in type 2 diabetes mellitus (T2DM) patients. One hundred and one T2DM patients and sixty healthy subjects were selected for this study. T2DM patients were further divided into controlled blood glucose (HbA1c < 7%, n = 46) and uncontrolled blood glucose (HbA1c ≥ 7%, n = 55) subgroups. All participants underwent conventional echocardiography and two-dimensional speckle-tracking echocardiography. Our results showed that an obvious difference was not observed in global longitudinal strain (GLS) between the controlled blood glucose group and the control group (− 20.34% vs − 21.22%, P = 0.068). Compared with the healthy controls, the uncontrolled blood glucose group showed an impaired GLS (− 18.62% vs − 21.22%, P < 0.001). Nevertheless, PSD was appreciably increased in the controlled blood glucose group (36.02 ms vs 32.48 ms, P = 0.01) and uncontrolled blood glucose group (57.51 ms vs 32.48 ms, P < 0.001). Multivariate linear regression analysis showed that HbA1c was closely related to PSD lesion in the LV in the T2DM group (β = 0.520, P < 0.001). PSD plays an important role in evaluating the coordination and synchronization of myocardial movement and provides a more accurate and sensitive index assessment of early LV systolic function in T2DM patients. In addition, HbA1c levels were related to LV dysfunction.


2020 ◽  
Vol 11 ◽  
Author(s):  
Fuqiong Chen ◽  
Jinsheng Lai ◽  
Yanfang Zhu ◽  
Mengying He ◽  
Huiying Hou ◽  
...  

Cardiomyopathy is the leading cause of increased mortality in diabetes. In the present study, we investigated the effects of decorin (DCN) gene therapy on left ventricular function, cardiac inflammation and fibrosis in type 2 diabetes. Type 2 diabetes was induced in male Wistar rats by high fat diet (HFD, 60% of calories as fat) and STZ (20 mg/kg, intraperitoneal). Diabetic rats were divided into (n=6 for each group) the control group, the GFP-treated group and the DCN-treated group, received intravenous injection of saline solution, recombinant adeno-associated viral (rAAV)-GFP, and rAAV-DCN, respectively. We evaluated cardiac inflammation, fibrosis, left ventricular function at 6 months after gene delivery. Results turned out that rAAV-DCN treatment attenuated diabetic cardiomyopathy with improved LV function compared with control animals, which might be related to the reduced cardiac inflammation and fibrosis. These protective effects were associated with TGFβ1 pathway (ERK1/2 and smad-2) and NF-κB pathway, which may due to the decreased activation level of IGF-IR, increased expression of PKC-α and Hsp70. In conclusion, our results show that rAAV-mediated DCN therapy may be beneficial in the treatment of Diabetic Cardiomyopathy.


2019 ◽  
Vol 1 (4) ◽  
pp. 120-126
Author(s):  
Wael Elfeky ◽  
Mohamed Aboelnasr ◽  
Ayman Sallam ◽  
Wael Haseeb ◽  
Dalia R El-Afify

Background: Myocardial injury during cardiac surgery is associated with increased morbidity and mortality, and proper myocardial protection improves surgical outcomes. We aimed to study the role of preoperative nicorandil in myocardial protection during valve replacement surgery. Methods: The study included 40 patients who were randomized into two groups: control group, and nicorandil group. Preoperative, intraoperative, and postoperative data were collected. Creatine kinase- MB (CK-MB), troponin I, malondialdehyde (MDA), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were measured 24-hours before surgery then 4, 12 and 48 hours after aortic cross-clamp removal. Results: Nicorandil significantly decreased MDA (p=0.005 and 0.036), TNF-α (p< 0.001), IL-6 (p<0.001 and 0.003) 4 and 12 hours following the removal of aortic clamp compared to the control group. Additionally, It significantly reduced CK-MB (p< 0.0001 and 0.0002) and troponin-I (p= 0.0002 and < 0.0001) 4 and 12 hours after the removal of the aortic clamp, respectively. However, there was no significant difference in MDA, TNF-α, IL-6, CK-MB, and troponin-I levels between the nicorandil and the control group after 48 hours following the removal of aortic clamping (p= 0.084; 0.64; 0.12; 0.12; 0.75; respectively). Conclusions: Nicorandil reduced myocardial injury significantly in valve replacement surgery. Nicorandil decreased CK-MB and troponin I and improved postoperative left ventricular ejection fraction.


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